Adaptive NKG2C(+)CD57(+) Natural Killer Cell and Tim-3 Expression During Viral Infections.
Adaptive NKG2C(+)CD57(+) Natural Killer Cell and Tim-3 Expression During Viral Infections.
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DOI：
10.3389/fimmu.2018.00686
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发表时间：
2018
影响因子：
7.3
通讯作者：
Larbi A
中科院分区：
文献类型：
--
作者：
Kared H;Martelli S;Tan SW;Simoni Y;Chong ML;Yap SH;Newell EW;Pender SLF;Kamarulzaman A;Rajasuriar R;Larbi A
人巨细胞病毒（HCMV）或人免疫缺陷病毒（HIV）等持续性病原体的重复刺激会诱导自然杀伤（NK）细胞的分化。这种成熟途径的特征在于获得表型标记物，CD 2，CD 57和NKG 2C，以及效应器功能-一个由Tim-3调节并由复杂的转录因子网络编排的过程，涉及T-bet，Eomes，Zeb 2，早幼粒细胞白血病锌指蛋白和Foxo 3。在这里，我们表明，在慢性病毒合并感染（HCMV，丙型肝炎病毒和艾滋病毒）的持续免疫激活干扰NK细胞的功能表型通过调节Tim-3途径; Tim-3表达的减少与抑制性受体的收购相结合，使NK细胞倾向于在慢性艾滋病毒感染的炎症环境中耗尽和细胞毒性表型。更好地理解NK细胞分化的机制可以帮助识别与慢性感染和癌症相关的检查点阻断疗法的新免疫靶点。
Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions—a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection. A better understanding of the mechanisms underlying NK cell differentiation could aid the identification of new immunological targets for checkpoint blockade therapies in a manner that is relevant to chronic infection and cancer.
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影响因子：
6.4
作者：
Cheng, Yong Q.;Ren, Jun P.;Yao, Zhi Q.
通讯作者：
Yao, Zhi Q.
影响因子：
4.3
作者：
Chen H;Lau MC;Wong MT;Newell EW;Poidinger M;Chen J
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Chen J
影响因子：
30.5
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Chiba, Shigeki;Baghdadi, Muhammad;Akiba, Hisaya;Yoshiyama, Hironori;Kinoshita, Ichiro;Dosaka-Akita, Hirotoshi;Fujioka, Yoichiro;Ohba, Yusuke;Gorman, Jacob V.;Colgan, John D.;Hirashima, Mitsuomi;Uede, Toshimitsu;Takaoka, Akinori;Yagita, Hideo;Jinushi, Masahisa
通讯作者：
Jinushi, Masahisa
影响因子：
6.7
作者：
Buggert M;Tauriainen J;Yamamoto T;Frederiksen J;Ivarsson MA;Michaëlsson J;Lund O;Hejdeman B;Jansson M;Sönnerborg A;Koup RA;Betts MR;Karlsson AC
通讯作者：
Karlsson AC
影响因子：
8.6
作者：
de Kivit, Sander;Lempsink, Ludwijn J. R.;Landay, Alan L.
通讯作者：
Landay, Alan L.